TDM Drugs commonly measured Cardioactive medications digoxin Antiseizure

TDM * Drugs commonly measured : • Cardioactive medications (digoxin) • Anti-seizure drugs (dilantin, Tegretol, Depakane, phenobarbital) • Antibiotics (amikacin, gentamicin, vancomycin) • Anti-cancer drugs (methotrexate) • Immunosuppressants (Cyclosporine, Tacrolimus) • Antidepressants (tricyclic antidepressants) • Lithium (bipolar disorder) • Bronchodilators (Theophylline)

TDM * Timing of Specimen Collections • Single most important factor in TDM • Steady state must be reached before TDM begins. • Usually draw at peak or trough • Peak for drugs given IV or if Pt has signs of toxicity shortly after dose • Majority drawn as trough • 처음 투약 시 or 투약방법이나 용량 변경시 • F/U TDM : 일정 시간에 채혈

TDM Ex) Digoxin - most good : trough level - Peak : oral dose 후 2 -3시간 ( tissue : 6 -10 시간) ∴ equilibrium betw plasma & tissue : 8 시간 이후 IV인 경우는 최소 4 시간 후 채혈 - therapeutic range : 0. 8 -2. 0 ng/ml - toxic Sx : > 2. 0 ng/ml in adults - consider : Renal func. 병용약물 (cyclosporin, quinidine, verapamil) Hthyroidism

약물 치료농도 독성농도 Phenobarbital 10 -30 ug/m. L >30 ug/m. L Phenytoin 10 -20 ug/m. L >20 ug/m. L Carbamazepine 4 -8 ug/m. L (병용 투여 시) 6 -12 ug/m. L (단독 투여 시) >15 ug/m. L Valproic acid 50 -100 ug/m. L >150 ug/m. L Digoxin 0. 8 -2. 0 ng/m. L >2 ng/m. L Cyclosporine Renal transplant 100 -400 ng/m. L(12 h) 100 -200 ng/m. L(12 h) Cardiac transplant 100 -300 ng/m. L (12 h) 100 -200 ng/m. L (24 h) BMT 100 -250 ng/m. L (12 h) MTX < 0. 02 umol/L (혈중 농도와 antineoplastic efficacy 간의 정확한 관련 성이 설정되어 있지 않다. ) >400 ng/m. L >5 -10 umol/L (24 h) >0. 5 -1. 0 umol/L (48 h) >0. 2 umol/L (72 h)

Tumor markers - 암세포에서 생성되어 분비되거나 암조직에 대한 반응으로 주위 정상조직에서 생성되는 생물학적 물질 - Tumor specific marker : 악성종양에서만 생성 Tumor ass. marker : 알려진 대부분의 markers 악성종양에서 양적 ↑ 정상인 or 양성질환에도 존재 Broad spectrum tumor marker (non-specific marker) : CEA, TPA, ferritin, β 2 m. . Organ specific tumor markers : AFP, PSA, CA 19 -9, CA 125, NSE

Tumor markers * Classification of tumor markers 1) Oncofetal Ag : AFP, CEA, SCC, TPA 2) Carbohydrate Ag Mucin markers : CA 125, CA 15 -3, CA 549, CA 27. 29, Du-PAN-2 Bl group Ag related markers : CA 19 -9, CA 15 -5, CA 50, CA 72 -4, CA 242 3) Enzyme : ALP, CK, LD (LD 5) NSE (NB, pheochromocytoma, SCLC) PAP, PSA 4) Hormones : ACTH, calcitonin, h. CG 5) Proteins : β 2 m, C-peptide, ferritin, Ig… 6) Genetic markers

* Tumor marker의 유용성 평가 1) Reference range vs Decision level 2) 예측치 모델 - sensitivity, specificity, predictive value - ROC curve : AUC - Which marker or which level ? Tumor markers

* Rec. for tumor marker Tumor markers 1) Never rely on single test result : serial test 2) same lab, same assay kit 3) Select highest marker before op. 4) Consideration of half-life 5) Multiple tumor markers : simultaneous test of CEA, CA 19 -9, CA 15 -3, CA 125 6) Use of non-specific marker : monitoring of Tx efficacy & recurrence : LD, CEA, TPA… 7) 대사, 배설 장기 고려

Tumor markers * PSA - Serine protease with chymotrypsin-like activity - tissue specific, non tumor specific BPH, prostatis, … - 전립선암 선별이나 조기 발견에는 효과적이지 못함 특히 gray zone 4 -10 ng/m. L에서 DDx 어려움 연령별 참고치, PSA density (= PSA/prostate vol)… - total PSA = complex form + free form 70 -90% 10 -30% ACT - free/total ratio at 4 -10 ng/m. L Free form ≥ 25% : Ca 가능성 ↓ ≤ 10% : Ca 가능성 ↑ PSA-ACT/total ratio ≥ 0. 66 : Ca 가능성 ↑

Tumor markers * AFP - 생후 18개월에 성인 level로 감소 , < 10 ng/m. L - 양성질환에서도 증가 – 간염, LC, 95% < 200 ng/m. L - preg. 때 증가 : 12주 증가 시작, 3 rd Δ 때 peak ( 300 ng/m. L ) - > 1000 ng/m. L Ca - 작고, 절제 가능한 HCC 검출 위한 cut-off : 10 -20 ng/m. L - AFP & h. CG : classification & staging of germ cell tumor

Tumor markers * CEA - nonspecific tumor maker - invasion & metastasis와 관련 - upper limit : 흡연자 5 ng/m. L, 비흡연자 3 ng/m. L - method dependent value - 양성질환 : LC, emphysema, 직장용종, 양성유방질환